Sentinel Oncology Limited

Cascadian Therapeutics, Inc.

Richard Justin Boyce

Robert George Boyle

David Winter Walker

Scott Peterson

Francine Farouz

Cong Hung Vo

The invention provides compounds of the formula (3): The compounds are useful in the treatment of cancers.

Pyrrole derivatives as PLK1 inhibitors

This invention relates to compounds that inhibit or modulate the activity of Chk-1 kinase. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds.

Pharmaceutical compounds

The invention provides compounds of the formula (3): or a pharmaceutically acceptable salt or tautomer thereof, wherein:Z is a 5-membered heteroaryl ring containing one or two nitrogen ring members and optionally one further heteroatom ring member selected from N and O;ring X is a benzene or pyridine ring;ring Y is a benzene, pyridine, thiophene or furan ring;Aris an optionally substituted benzene, pyridine, thiophene or furan ring;m is 0, 1 or 2;n is 0, 1 or 2;Ris selected from various substituents:Ris selected from hydrogen and a Chydrocarbon group;Ris selected from hydrogen and a Chydrocarbon group;Ris selected from various substituents;Ris selected from various substituents;Aris an optionally substituted phenyl, pyridyl or pyridone group;Ris a group Q-R&#x2014;R;Qis absent or is a Csaturated hydrocarbon linker;Ris selected from O; C(O); C(O)O; CONR; N(R)CO; N(R)CONR, NR; and SONR;Ris selected from hydrogen and various substituents;and Ris selected from R. The compounds are useful in the treatment of cancers.

The invention provides compounds which inhibit or modulate the activity of Chk-1 kinase and which are useful in the treatment of cancer. The compounds have the general formula (1): and salts, N-oxides and tautomers thereof, wherein m is 2, 3 or 4; n is 0 or 1; Qis selected from a bond; C(&#x2550;O); S(O); SO; and an alkylene chain of 1 to 4 carbon atoms in length between the moiety Rand the nitrogen atom. N, wherein (a) one or more of the 1 to 4 carbon atoms of the alkylene chain may optionally be substituted with one or two Calkyl groups; and/or (b) one carbon atom of the 1 to 4 carbon atoms of the alkylene chain may optionally be replaced by a cyclopropane-1,1-diyl or 1,1-cyclobutanediyl group; and/or (c) one carbon atom of the 1 to 4 carbon atoms of the alkylene chain may optionally be replaced by C(&#x2550;O), S(O), or SO, provided that Qcontains no more than one C(&#x2550;O), S(O), or SOmoiety; Ris selected from hydrogen, methyl, chlorine and bromine; Ris selected from hydrogen, methyl, methoxy and a group &#x2014;(O)-Q-R; Ris selected from hydrogen, a group Hyd, a group &#x2014;O-Hydand a group &#x2014;(O)-Q-R; provided that when one of Rand Ris &#x2014;(O)-Q-R, the other is selected from hydrogen, methoxy and methyl; and Ris selected from amino, NH-Hyd, N(Hyd); and a non-aromatic carbocyclic or heterocyclic ring of 4 to 7 ring members containing 0, 1, 2 or 3 heteroatom ring members selected from O, N and S and oxidized forms thereof; the carbocyclic or heterocyclic ring being optionally substituted with one or two substituents R. Also provided are pharmaceutical compositions containing the compounds and methods for making the compounds.

Growing community of inventors

Newmarket, United Kingdom

Richard Justin Boyce